Chemotherapy of murine colorectal carcinoma with cisplatin and cisplatin plus 3'-deoxy-3'-azidothymidine.

Abstract

In light of the discouraging results obtained with conventional chemotherapy of human colon cancer using 5-fluorouracil, we examined the effects of cis-diamminedichloroplatinum (cisplatin) alone and combined with 3'-deoxy-3'-azidothymidine (AZT) on chemotherapy of colorectal adenocarcinomas induced by dimethyldrazine in CD-1 mice. Thirteen weeks after a 20 week tumor induction period (15 mg/kg dimethylhydrazine weekly) groups of 19 mice were given either no therapy, or weekly cisplatin (6 mg/kg for 4 wks), AZT (400 mg/kg, wks 3 and 4), or cisplatin and AZT. Animals were autospied at death or after euthanasia on day 99 post initiation of therapy, their colons excised, fixed in buffered formalin and the number and volume of tumors measured. Cisplatin alone or with AZT decreased tumor size by 47-52%, and enhanced survival, leaving 55% of the mice alive at day 99 compared to 18% in controls. These therapeutic effects were amplified when animals were given chemotherapy during recovery from the effects of short-term dietary provision of the anti-carcinogenic steroid, dehydroepiandrosterone (DHEA). Our results suggest cisplatin is an effective chemotherapeutic agent against colon cancer in this murine model, and warrant further studies of its interaction with AZT and DHEA in enhancing this effect.